Between the Devil and the Deep Blue Sea: Non-Coding RNAs Associated with Transmissible Cancers in Tasmanian Devil, Domestic Dog and Bivalves

Lister, Nicholas C.; Milton, Ashley M.; Hanrahan, Benjamin J.; Waters, Paul D.

doi:10.3390/ncrna7040072

Cited by 2 publications

(2 citation statements)

References 143 publications

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“…Originating in one animal, viable cancer cells are directly transmitted into unrelated hosts in a process similar to metastasis [ 21 , 22 ]. Transmissible cancers have been observed in domestic dogs, the Tasmanian devil, hamsters and six bivalve species such as the soft-shell clam [ 23 ]. Canine transmissible venereal tumors (transmitted during sexual intercourse) may have originated thousands of years ago from the cells of a wolf or East Asian breed of dog [ 21 – 25 ].…”

Section: Hierarchical Model Of Hallmarks Of Cancer: Arranging the Ora...mentioning

confidence: 99%

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Hallmarks of cancer and hallmarks of aging

Blagosklonny

2022

Aging

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A thought-provoking article by Gems and de Magalhães suggests that canonic hallmarks of aging are superficial imitations of hallmarks of cancer. I took their work a step further and proposed hallmarks of aging based on a hierarchical principle and the hyperfunction theory. To do this, I first reexamine the hallmarks of cancer proposed by Hanahan and Weinberg in 2000. Although six hallmarks of cancer are genuine, they are not hierarchically arranged, i.e., molecular, intra-cellular, cellular, tissue, organismal and extra-organismal. (For example, invasion and angiogenesis are manifestations of molecular alterations on the tissue level; metastasis on the organismal level, whereas cell immortality is observed outside the host). The same hierarchical approach is applicable to aging. Unlike cancer, however, aging is not a molecular disease. The lowest level of its origin is normal intracellular signaling pathways such as mTOR that drive developmental growth and, later in life, become hyperfunctional, causing age-related diseases, whose sum is aging. The key hallmark of organismal aging, from worms to humans, are age-related diseases. In addition, hallmarks of aging can be arranged as a timeline, wherein initial hyperfunction is followed by dysfunction, organ damage and functional decline.

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Section: Hierarchical Model Of Hallmarks Of Cancer: Arranging the Ora...mentioning

confidence: 99%

“…[ 26 ]. Derived from a single original clam, leukemia-like cancer spreads among marine bivalves through sea water, leading to massive population loss [ 23 , 27 ].…”

Section: Hierarchical Model Of Hallmarks Of Cancer: Arranging the Ora...mentioning

confidence: 99%

Hallmarks of cancer and hallmarks of aging

Blagosklonny

2022

Aging

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Divergent DNA methylation patterns and gene expression in MYC and CDKN2B in canine transmissible venereal tumors

Keopaseuth,

Pringproa,

Patchanee

et al. 2024

Vet World

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Background and Aim: Canine transmissible venereal tumor (CTVT), a unique transmissible cancer in dogs, affects the external genitalia and potentially spreads to other parts of the body. While somatic mutations in oncogenic and tumor-suppressing genes are linked to CTVT development, the impact of DNA methylation, which affects gene expression, remains unclear. This study explored whether DNA methylation in the promoter regions of the MYC oncogene and CDKN2B tumor suppressor genes in CTVTs is associated with their expression, both at the gene and protein levels. Materials and Methods: To investigate promoter DNA methylation of MYC and CDKN2B in CTVTs, we analyzed frozen tissue samples from genital CTVT (GTVTs) and extragenital CTVT (ETVTs). Genomic DNA was extracted, bisulfite-treated, and analyzed using bisulfite polymerase chain reaction (PCR) and sequencing. The messenger RNA and protein of MYC and CDKN2B were also extracted and assessed by real-time PCR and Western blotting. Matching formalin-fixed, paraffin-embedded blocks were used for immunohistochemical staining to visualize protein distribution in GTVT and ETVT tissues. Results: Although both GTVT and ETVT samples showed MYC promoter methylation, the extent of methylation differed significantly. GTVTs displayed a much higher degree of methylation, potentially explaining the more pronounced downregulation of MYC gene expression and reduction in c-MYC protein levels observed in GTVTs compared with ETVTs. Our data revealed a prevalent hypermethylation pattern in the CDKN2B promoter across both sample types. However, DNA methylation, which was expected to have a suppressive effect, did not correlate with gene/protein expression. GTVTs displayed high protein levels despite significantly reduced CDKN2B expression. Conversely, ETVTs maintained regular CDKN2B expression but exhibited reduced protein production, suggesting a complex interplay between methylation and expression in these tumors. Conclusion: MYC demonstrated a clear association between its promoter methylation status, gene expression, and protein levels; however, CDKN2B lacked this correlation, implying the involvement of methylation-independent regulatory mechanisms and highlighting the need for further investigation. Keywords: canine transmissible venereal tumor, CDKN2B, DNA methylation, MYC, oncogene, tumor suppressor gene.

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Between the Devil and the Deep Blue Sea: Non-Coding RNAs Associated with Transmissible Cancers in Tasmanian Devil, Domestic Dog and Bivalves

Cited by 2 publications

References 143 publications

Hallmarks of cancer and hallmarks of aging

Hallmarks of cancer and hallmarks of aging

Divergent DNA methylation patterns and gene expression in MYC and CDKN2B in canine transmissible venereal tumors

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